JPS6247546B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to compositions that form strong bonds with bone tissue and have a porous, high specific surface, silicon-rich surface or are capable of producing such a surface in vivo. These compositions are therefore excellent materials for dental and surgical fillings or coatings thereof. Biologically active silicon dioxide (silica) based glasses and glass-ceramics are known in the art. These materials are characterized by their ability to form direct chemical bonds of excellent strength with bone in vivo. The strength of this bond does not strongly depend on the degree of crystallinity of the biologically active material. However, the use of partially or fully crystallized glass-ceramics is often preferred since devitrification increases the strength of the biologically active material itself. A variety of dental and surgical fillings for cementless filling processes are made from these biologically active glasses and relatively strong materials such as glass-ceramics and aluminum oxides as well as "surface-coated surgical filling alloys." It is proposed to configure The silica-based biologically active glasses and glass-ceramics according to the prior art generally contain about 40-60% by weight of silica as a network former, in addition to significant amounts of soluble modifiers such as sodium oxide, Contains potassium oxide, calcium oxide, magnesium oxide, phosphorus pentoxide, lithium oxide and calcium fluoride. Boron oxide may be substituted for some silicon dioxide. A particularly preferred composition according to the prior art called composition 45S5 (trade name) contains 45% by weight silicon dioxide, 24.5% by weight sodium oxide, 24.5% by weight calcium oxide, and 6% by weight phosphorous pentoxide. . The chemical bond between the biologically active glass or glass-ceramic material and the bone is formed by ingrowth and interlocking of bone tissue within the macroscopically porous filling surface. should be distinguished from mechanical type connections. To date, it has been generally believed that biologically active glass or glass-ceramic materials are active due to the reactivity of their surfaces in biological solutions. That is, soluble ions such as sodium and calcium ions are selectively eluted from the glass or glass-ceramic material, thereby rendering the surrounding biological fluid alkaline. The alkaline solution then attacks the glass or glass-ceramic material and forms a silica gel layer thereon. According to the mechanism proposed here, it is to this silica gel layer that this newly growing bone attaches [Hench, LL, et al.
Splinter, R.J., Allen, W.C. and Greenlee, T.
K., J.Biomed.Mater.Res.Symp.No.2 (Part
), pp. 117-141 1971; Hench, LL, and
Paschall, H. A., J. Biomed. Mater. Res. Symp.
No. 4, pp. 25-42 1973; Hench, LL and
Paschall, H.A., J. Biomd, Mater.Res.Symp.,
No. 5 (Part) pp. 49-64 1974; Piotrowski,
G., Hench, L.L., Allen, W.C. and Miller, G.
J., J. Biomed. Mater. Res. Symp., No. 6, No. 47~
61 pages 1975; Clark, AE, Hench, LL and
Paschall, H.A., J.Biomed.Mater.Res., 10th, No.
Pages 161-174 1976; US Special No. 3919723, US Special No.
No. 3922155, US Special No. 3981736, US Special No. 3987499
No., US Patent No. 4031571 specifications]. It is, of course, known that dental or surgical fillings may be secured to a patient's bone through the use of organic resin cements such as polymethyl methacrylate. However, drawbacks with respect to bioreactivity, toxicity and loosening of the fixation are known in the use of such cements. It is also known to strengthen filled resin cements by incorporating various types of reinforcing agents, including glass particles (see US Pat. No. 3,919,773). Glass-reinforced hardened inorganic cements (eg Portland cement) are also known (see US Pat. No. 3,147,127). A novel dental or surgical filling having a surface that binds to a patient's bone has now been discovered, in which the binding surface or bonding surface comprises at least about 80% by weight silicon dioxide and at least Approximately 80
It is comprised of a biocompatible glass, glass-ceramic material having a specific surface of m ² /g, a porosity of about 10 to about 50% by volume, and an average pore size of about 20 to about 300 Å. The present invention also provides that the bonding surface is an inorganic material other than a silicon dioxide-based glass or glass-ceramic containing up to about 80% silicon dioxide, and that has physical properties suitable for the purpose. dental or surgical fillings having surfaces that bond to the patient's bone and are made of such inorganic materials that are chemically compatible with tris(hydroxymethyl)aminomethane buffer at 37°C at a pH of 7.2. A porous silica-rich surface layer with a specific surface of at least about 80 m ² /g can be produced during about 10 days of exposure to an aqueous solution. Materials encompassed by this second aspect of the invention include certain ceramics and hardened inorganic cements such as Portland cement. Additionally, the present invention encompasses an improved method for fixing dental or surgical fillings to bone, which comprises placing wet cement between the surface of the bone and the filling and allowing the cement to harden. In this improved method, approximately 10% of
It consists of using a biologically compatible inorganic cement capable of producing a porous silica-rich surface layer with a specific surface of at least about 80 m ² /g during exposure for days. Portland cement is one type of inorganic cement that can be used. In a preferred embodiment of the improved method, the wet cement is mixed with biologically active silicon dioxide-based glass or glass-ceramic particles. In another preferred embodiment, the bonding surface of the filling in contact with the inorganic cement consists of a biologically active silicon dioxide-based glass or glass-ceramic. Biologically active silica-based glasses and glass-ceramic materials produced by standard casting and crystallization methods have a porous silica-rich surface layer with at least some minimum specific surface that can be deposited in vivo. It has now been unexpectedly discovered in the present invention that the ability to bond strongly to bone by virtue of its ability to occur in the present invention. Silica-based glasses and glass-ceramic materials that do not form a surface layer with the above properties in vivo generally form only poor or no chemical bonds with bone. This silica-rich surface layer with a high surface area (approximately 25-100 microns thick) provides a vast number of sites for the deposition and interaction of various organic and inorganic components of healing bone. It is thought that it will provide the following. Biological activity in vivo can be assessed by convenient in vitro tests. That is, a silica-based glass or glass-ceramic can absorb a minimum of about 80 m ² per gram of its layer during its exposure to an aqueous tris(hydroxymethyl)aminomethane buffer at a pH of 7.2 and a temperature of 37°C for about 10 days. If a porous silica-rich surface layer with a specific surface can be produced, it will bond strongly to bone in vivo. The table presents data for a series of non-porous glasses based on the silicon dioxide-calcium oxide-sodium oxide-phosphorus pentoxide system. The biological activity depends strongly on the silicon dioxide content, but not so much on the contents of the other three components. It has been found that when the weight ratio of calcium oxide:sodium oxide is about 0.4 to about 2.5 and the phosphorus pentoxide content is 6% by weight, the boundary of biological activity is between about 54 and 58% by weight of silicon dioxide. Ta. This marginal range drops to about 45-55% by weight when phosphorus pentoxide is removed.Replacing sodium oxide with potassium oxide has little effect on biological activity. Silicon dioxide-sodium oxide glasses containing greater than about 78% silicon dioxide by weight did not bond to bone. Substantially pure silicon dioxide glass also did not bond. The glasses in the table are reagent grade carbon calcium, sodium carbonate, potassium carbonate,

【table】

[Table] Produced by melting a mixture of phosphorus pentoxide and 5 μm silicon dioxide powder at about 1200-1500°C, casting a disc-shaped sample, and then tempering the sample at about 450-700°C. A 4 x 4 x 1 mm filler was then prepared for rat tibia mini push out testing for biointegration into bone as described below. The table demonstrates the strong dependence of biological activity on the surface generated in vitro. Thus, if the non-porous glasses of this system contain too much SiO ₂ , they will not be able to produce a surface layer suitable for bonding to bone in vivo, as shown in in vitro studies. This surface area is B for a critical point (CO ₂ ) dried glass sample.
Obtained by ET nitrogen adsorption method and shown in increased magnification. Direct measurements of the surface when measured independently show that a 1000-fold increase in surface area for the entire sample corresponds to a production of about 80 m ² of specific surface per gram of dry surface material. The presence or absence of integration with bone was determined using the known rat tibial mini push-out test. This test utilizes the following procedure. Packings with dimensions of 4 x 4 x 1 mm are prepared for each composition to be tested. each sample
Wet polish with 180, 320 and 600 grit silicon carbide polishing discs. A final dry sanding with a 600 grit disk is followed by a 2 minute ultrasonic cleaning in reagent grade acetone. The filling is then wrapped in surgical drapes and gas sterilized with ethylene dioxide. Male Sprague-Dawley rat (weight 150-300)
g) are used as test animals. Sodium pentabarbital is administered intraperitoneally to anesthetize the animal. Inject 0.1 ml of atropine subcutaneously to prevent tracheal congestion. Make an incision on the front of the left hind leg from the knee to the middle of the tibia. The peroneus muscle on the side of the tibia is cut from its root and removed from the bone. Separate the anterior tibia and common extensor muscles from the midsection of the tibia. A groove is made in the lateral and medial cortex of the anterior periphery of the tibia using a compressed nitrogen gas powered Halldrill with a carbide-tipped dental burr. A filling material is inserted into the defect and the incision is sutured. The relative dimensions of the filling and the tibia are such that the filling slightly protrudes to one side of the tibia after filling. Testing for bone integration 30 days after filling provides a reliable test of bonding ability. After sacrifice, the test tibia is examined for each animal and any attached soft tissue is removed. Measure the area on the exposed end of each filling and remove boney overgrowths. This is done to prevent unwanted mechanical interference. The mechanical integrity of the bone is then tested. Apply a push-out load of approximately 30 Newtons onto the filling using modified sponge tweezers. If this filling resists movement under the applied load, it is considered to have passed the mini push-out test for the bond. If any movement is observed between the filling and the surrounding bone, the bone is considered to have failed the test. What is even more surprising is that bones have a porous silica-rich surface layer with at least a certain minimum specific surface before filling, or that all inorganic biological organisms produce a surface layer of the above properties in vivo. compatible materials (this material is compatible with silicon dioxide-based glasses and glass-
The discovery was made that it strongly binds to ceramics (including but not limited to ceramics). The unifying property of materials with these biological activities (i.e., the ability to form strong chemical bonds with bone in vivo)
characteristics) that allow for the desirable high surface area, porous, silica-rich surface layer to be utilized for growing bone. Neither calcium, sodium nor phosphorus compounds are essential components of the biologically active material, except to the extent that soluble modifiers may contribute to the in vivo production of the required surface layer.
Biological activity is assessed by BET nitrogen adsorption analysis of the material itself or, if the required surface layer occurs in vivo, by BET nitrogen adsorption analysis of the treated sample according to the in vitro test described above. sell. Here, the surface area is 1g of the surface material based on the lightweight standard.
It is expressed in square meters per square meter (m ² ). A surface area of 80 m ² /g can be generated in as little as 6 hours depending on the material tested. If the biologically active material contains both soluble calcium ions and soluble ions containing phosphorus and oxygen, calcium phosphate or related compounds will be present on the outermost silica-rich surface layer both in vivo and in vitro as described above. Deposit quickly. This deposit is generally formed from ions generated by the biologically active material itself, which appears to favor in vivo activity. The presence of such a deposition phenomenon does not essentially affect the results of the BET analysis regarding the increase in surface area after the reaction. As defined herein, the term glass refers to an inorganic material that is primarily glassy, while glass-ceramic refers to a glass that is devitrified by about 20-100% by volume. The term cement refers to a composition that can be used to harden with different articles depending on its hardening ability. The term ceramic refers to polycrystalline ceramic materials other than glass-ceramic. Chemical bonding between bone and biologically active materials can be achieved through large (approximately 10 to 200 μm) of certain known filling materials.
It is important to distinguish this from mechanical bonding, which occurs due to the interlocking of bone tissue within the surface pores of the bone. The direct chemical bonding of the biologically active materials described herein with bone occurs through chemical forces and is broadly primary (e.g., ionic, covalent, oriented overgrowth) and secondary (e.g., Phandel). Defined to include chemical bonds (Wahls, hydrogen bonds, London dispersion forces). The required porosity of the silica-rich surface layer is of a different nature than the porosity present in mechanically interlocking fillings for bonding to bone. A pore size of at least about 50 μm is required for substantial ingrowth of hard tissue to occur. However, in the present invention, the active silica-rich surface layer generally has a pore size of about 3000 Å or less, which is too small for substantial ingrowth of growing bone tissue to occur. The invention therefore does not suffer from the known drawbacks of mechanical interlocking within porous matrices, ie the loss of strength resulting from voids left unoccupied by growing bone. As defined herein, the term dental filling means, for example, a denture, a dental crown, an inlay, and the like. The term surgical filling refers to bone pins, bone plates, bone replacement prostheses, bone replacement prosthetics (e.g. hip joint prostheses), or any other surgical filling or prosthesis that is to be connected directly to the patient's bone. means.
Of course, the biologically active material used in each case must be biologically compatible and have suitable physical properties for the purpose, such as strength, friction resistance, fatigue resistance,
It will be necessary to have elastic modulus, ductility, etc. As used herein, the term biocompatible means that the material is benign or non-toxic in the in vivo biological system in which it is used and does not adversely affect bone growth processes. The last column of the table indicates that substituting magnesium oxide for calcium oxide, at least in some circumstances, will likely inherently alter the Ca:Mg ratio in surrounding body fluids, thus making silica-based materials less biologically viable. Indicates that they are incompatible. All bonding surfaces of the filling, ie, the surfaces that contact the patient's bone for bonding, must be biocompatible. However, in some cases some such binding surfaces may be biocompatible but inert. Thus, for example, the scope of the invention includes fillers made of or coated with phase-separated glass or glass-ceramic materials, which contain active (high surface area produced in vivo) and inert (high surface areas produced in vivo). In this case, materials with a specific surface area of approximately 80 m ² /g or less may be included. . The invention also encompasses fillings in which the portion of the surface in contact with the patient's bone is, for example, a biocompatible but inert metal or ceramic. In one aspect of the invention described herein, the bonding surface of the dental or surgical filling comprises at least about 80% by weight silicon dioxide and has a specific surface of at least about 80 m ² /g;
A biocompatible glass, glass-ceramic, or ceramic material having a porosity of about 10 to about 50% by volume and an average pore size of about 20 to about 300 Å, with some pores up to about 3000 Å in diameter. Consisting of It should be noted that the surface textures shown here are present on the surface material itself prior to biofilling. That is, there is no need for the material to be surface-reactive or to be subjected to selective elution in a physiological solution. This observation is quite surprising and unexpected. The advantages of using glass, glass-ceramic, or ceramic in this embodiment of the invention are its low cost and the fact that very little (or virtually no) ionic substances elute from the material into the body. There is no need for the material of this aspect of the invention to contain calcium or phosphorus compounds. Accordingly, a group of these materials comprises those containing less than about 0.1% by weight of phosphorus on an elemental basis. Different groups of these materials have a minimum of approx.
It comprises 95% by weight silicon dioxide, less than about 1% by weight calcium, and less than about 0.1% by weight phosphorus. In another embodiment, the material, preferably glass, contains at least about 80% by weight silicon dioxide, about
Consisting of less than 20% by weight boron oxide. An example of a useful biologically active material is Thirsty Glass (Corning Glassworks,
Corning, New York), a highly porous glass consisting primarily of silicon dioxide and boron oxide. Thirstay glass is an acid-leached product of the phase-separated borosilicate glass from which it was made. Surgical or dental fillings according to embodiments of the invention may consist of a single glass, glass-ceramic filling or a matrix material coated with a biologically active material, or may be of any known type. But that's fine. Known casting, crystallization and sintering methods may be used to manufacture single fillings such as dentures. If a strength greater than that exhibited by the biologically active material itself is required, metals used in known metallization processes (e.g., Vitallium, a trademark of Howmedica LNC., New York, New York) may be used. Non-biologically active ceramics or other substrates can be used in coating techniques such as firing, dipping, coating and sintering, flame spraying, and the like. A particularly advantageous method of coating biologically active glass or glass-ceramic with an alumina matrix is described in U.S. patent application Ser.
It is disclosed in the specification of No. 766749. A particularly advantageous method of coating with biologically active glasses or alloys of glass-ceramic materials is disclosed in US Pat. No. 798,671. When a glass-ceramic coating is desired, the devitrification is carried out by known methods, but the devitrification can be carried out either before or after the coating is applied to the substrate. For example, a packing consisting of a matrix or coating of borosilicate glass, in which only the surface of the matrix or coating is eluted, making that surface biologically active, is within the scope of the invention. In another embodiment of the invention, the bonding surface of the dental or surgical filling is a silicon dioxide-based glass or glass containing up to about 80% silicon dioxide by weight.
All biologically compatible inorganic materials other than "ceramics" (of which certain types are known), which have been shown to exhibit a minimum A porous silica-rich surface layer with a specific surface of about 80 m ² /g can be produced. This material can be, for example, a hardened mineral cement, ceramic, glass, glass-ceramic or belongs to all other classes. For example, in the case of Portland cement, the in vivo surface layer contains significant amounts of other inorganic oxides (i.e. alumina and iron oxides) and silica. Because of the fact that fills containing these other inorganic oxides are within the scope of this invention, an example of a biocompatible hardened inorganic cement is Portland cement, which has the following composition ( dry weight basis) SiO ₂ 20-24% by weight Fe ₂ O ₃ 2-4% by weight Al ₂ O ₃ 1-14% by weight CaO 60-65% by weight MgO 1-4% by weight SO ₃ 1-1.8% by weight and a specific surface (cured) of 200 m ² /g.The filling may be made of a single material or a biologically active material, such as ceramic or non-biologically active ceramic coated with cement, an organic polymer, It may also be comprised of a matrix of other materials such as plastic or metal (e.g., Vitallium (a trade name of Haumedica Inc., New York, NY). Single articles of cement, ceramic or other materials known in the art may be used. Any method of manufacturing or coating a matrix material with them, or any other form useful as a filler, may be used in carrying out embodiments of the present invention. The hardening of the cement can occur either before or after filling; thus, in one aspect of the invention, the bone substitute prosthesis involves inserting moist cement into the void in the patient's bone created by the removal of diseased or injured bone. The surgical or dental filling is manufactured by forming the cement into the desired shape and curing the cement in situ. In yet another aspect of the invention, the surgical or dental filling comprises a wet-setting inorganic cement. The bonding surface of the filling, i.e. the surface that contacts the cement for bonding to the patient's bone, is preferably a biologically active silicon dioxide based glass or The cement consists of glass-ceramic.This cement, in its hardened state, has been shown to exhibit at least approximately
It can produce a porous surface layer rich in silica with a specific surface of 80 m ² /g. When this cement hardens in vivo, it produces a biologically active, high specific surface, silica-rich porous surface layer, so that it forms an extremely strong bond with bone. With this surface it forms a very strong bond between the filling and the biologically active glass or glass-ceramic surface. Of course, this hardened cement material is inherently strong in itself. Therefore, there are various problems associated with the use of polymethyl methacrylate resin cement, namely toxicity problems;
In vivo relaxation and reactivity problems can be reduced. In another preferred embodiment, the cement not only enhances its strength itself, but also improves the respective strength of the bone-cement and filler (biologically active as described above)-cement bond. It is reinforced with biologically active, silicon dioxide-based glass or glass-ceramic particles. The following examples are illustrative of the invention but should not be considered limiting. Example 1 4x4x1 of Thirstay Glass (Corning Glass Works, Corning, New York)
mm fills were prepared and wet polished with 320 and 600 grit silicon carbide polishing discs. They were then ultrasonically cleaned in distilled water and sterilized by boiling. The Thirstay glass sample used consisted of approximately 96% by weight silicon dioxide and 4% by weight boron oxide;
Specific surface of 200m ² /g, porosity of 28% by volume and 40Å
It had an average pore size of This filling was tested for in vivo bone integration by a rat tibia mini push-out procedure known in the art. After filling
No bond was observed between the bone and the filler at 11 or 18 days. However, 40 days after filling, two out of two fills passed this mini-pushout test for bonding. When one of these fillings was sectioned and examined by microscopy, it was shown that a direct chemical bond had formed between the Thirst Glass filling and the healing bone. Example 2 The dry Portland cement used in this example experiment was an American Society for Testing material type.
Testing Materials Type) Portland cement. Water was added to the cement to give a water to cement ratio of 0.4, and the mixture was cured for about 2 weeks to 30 days to produce cured samples.
After hardening, 4 x 4 x 1 mm fillings were made from the cement. These were wet polished with 320 and 600 grit silicon carbide polishing discs. The packing was then rinsed in distilled water and placed in the wash solution until filling. In-vivo testing for bone attachment was performed by the rat tibia mini-push-out method known in the art. No binding was observed even after 10 and 13 days after filling. However, 28 days after filling, 2 out of 2 samples passed this mini-pushout test for bonding. One out of every sample passed this mini-pushout test 69 days after filling. One out of every sample passed this mini-pushout test 92 days after filling. Qualitative mechanical testing of the filler-bone joint after 92 days showed cracks within the bone or filler, but no cracks at the interface between the two materials. Microscopic examination showed that there was a direct bond between the pre-hardened Portland cement filling and the healing bone.

Claims (1)

[Scope of Claims] 1. A dental or surgical filling having a surface for bonding to the patient's bone, the bonding surface consisting of a biologically compatible glass, glass-ceramic or ceramic material, The chemically compatible glass, glass-ceramic or ceramic material contains at least about 80% by weight silicon dioxide and has a specific surface of at least about 80 m ² /g, from about 10 to about 50% by volume.
The above-mentioned filling is characterized in that it has a porosity of about 20 to about 300 Å and an average pore size of about 20 to about 300 Å. 2. The filling of claim 1, wherein the ceramic material contains less than about 1% by weight of calcium and less than about 0.1% by weight of phosphorous. 3. A filling according to claim 2, wherein the ceramic material contains at least about 95% by weight silicon dioxide. 4. The filling of claim 1, wherein the ceramic material contains less than about 20% by weight boron oxide. 5. The filling according to claim 4, wherein the ceramic material is glass.